Mexiletine, 1-(2,6- dimethyl-phenoxy)-2-propanamine, is an approved and well-known pharmaceutical useful as an anti-arrhythmic. Its structure and use are described in U.S. Pat. Nos. 3,659,019 and 3,954,872. Pharmaceutical formulations comprising mexiletine are described in U.S. Pat. No. 4,031,244.
Mexiletine hydrochloride is a finely divided, crystalline substance and is used in commercial pharmaceutical formulations for mexiletine. However, the hydrochloride has a low bulk density, and so consequently also provides a large bulk volume. One commercial mexiletine product, sold under the trademark MEXITIL by Boehringer Ingelheim Pharmaceuticals, Inc., is a capsule where the hydrochloride represents approximately 62% (w/w) of the fill weight of the capsule. The inert excipients in the MEXITIL product include corn starch (bulking agent and granulation aid), colloidal silicon dioxide (drying agent and to prevent granulation caking), and magnesium stearate (lubricant). During processing to manufacture the MEXITIL product, a 1:1 solution of purified water and SD3A (specifically denatured ethanol for pharmaceutical use) alcohol is prepared. This solution is then used to increase the density of the above-mentioned MEXITIL ingredients (except magnesium stearate). The wetted combination is then dried (to evaporate or remove the water/denatured ethanol), sized by milling and then combined with the lubricant magnesium stearate. This final blend is then filled into capsules.
As indicated above, a solution of water and denatured ethanol is prepared in order to increase the density of the mexiletine hydrochloride blend. This is necessary in order to produce a powder that can be effectively handled and placed into capsules. Use of water alone does not achieve the necessary and required densification of the powder blend. However, current and future environmental regulations restrict the amount of organic solvent emissions into the atmosphere. Accordingly, the current manufacturing process for the MEXITIL product will become more costly and less efficient as such emissions become more restricted.
A dry, granulation process involving roller compaction results in a powder blend of mexiletine hydrochloride suitable for use in capsules. Dry granulation and compaction does not result in emission of organic solvents into the atmosphere.